Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia

Kowalczyk-Quintas C, Willen L, Anh Thu Dang , Sarrasin H, Tardivel A, Hermes K, Schneider H, Gaide O, Donze O, Kirby N, Headon DJ, Schneider P (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Journal of Biological Chemistry American Society for Biochemistry and Molecular Biology

Publisher: American Society for Biochemistry and Molecular Biology

Book Volume: 289

Pages Range: 4273-85

Journal Issue: 7

DOI: 10.1074/jbc.M113.535740

Abstract

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated.

Authors with CRIS profile

Katharina Hermes Professur für Kinderheilkunde/Experimentelle Perinatalmedizin Holm Schneider Professur für Kinderheilkunde/Experimentelle Perinatalmedizin

Involved external institutions

Université de Lausanne (UNIL) CH Switzerland (CH) Adipogen AG CH Switzerland (CH) Edimer Pharmaceuticals US United States (USA) (US) University of Edinburgh GB United Kingdom (GB)

How to cite

APA:

Kowalczyk-Quintas, C., Willen, L., Anh Thu Dang, ., Sarrasin, H., Tardivel, A., Hermes, K.,... Schneider, P. (2014). Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia. Journal of Biological Chemistry, 289(7), 4273-85. https://doi.org/10.1074/jbc.M113.535740

MLA:

Kowalczyk-Quintas, Christine, et al. "Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia." Journal of Biological Chemistry 289.7 (2014): 4273-85.

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